During acupuncture treatment, acupuncture needles are inserted and manipulated until a characteristic local tissue reaction termed "de qi" is observed. De qi can be perceived by the acupuncturist in the form of "needle grasp", a mechanical gripping of the needle by the tissue. De qi is considered essential to the therapeutic effect of acupuncture. Therefore, we believe that understanding this local tissue reaction will lead to an understanding of how the therapeutic effect of acupuncture therapy arises. We suggest that the following mechanism underlies needle grasp: needle manipulation causes winding of collagen and elastic fibers around the needle; this induces tension in the collagen network surrounding the needling site; this mechanical signal is then transduced into local cells causing changes in actin- polymerization and gene expression. The objective of the current work is to develop the tools needed to evaluate this mechanism. Scanning acoustic microscopy and elastography are recently developed ultrasound imaging techniques that can quantify a tissue's mechanical behavior. We propose to use these techniques in the following ways: In vitro study of rat skin tissue exolants: A scanning acoustic microscope (C-scan) will be used to visualize and quantify anatomical and biomechanical changes occurring within the various layers of skin and underlying tissue as a result of acupuncture needle manipulation. After ultrasound scanning, conventional histology will be performed for correlation with ultrasound-derived images. In vivo study of human volunteers: Clinical ultrasound imaging and elastography techniques will be used to visualize and quantify changes in the elastic properties of skin and subcutaneous tissue as a result of acupuncture needle manipulation. Once these tools ere fully developed we plan to use them in future works in the following ways: 1) combine C-scan ultrasound with 3-D reconstruction image analysis of rat skin tissue explants; 2) combine in vivo ultrasound elastography with skin punch biopsies in humans: histochemistry will allow us to study the potential mechanotransduction effect of needle grasp on cells within connective tissue; 3) use of the above in vitro and in vivo experimental systems to study biophysical and biochemical factors that modulate needle grasp; 4) compare needle grasp in normal human subjects vs. patients with different types of chronic pain syndromes.